Retinal ischemic injury contributes to visual loss in may diseases (eg, diabetes and artherosclerosis) and is a problem of major proportions in our society. The underlying pathophysiologic mechanisms are poorly understood, and current treatment is inadequate. The long-term objective of this application is to overcome these deficiencies. The experimental approach employs vitreoperfusion, a new procedure in which the vitreous cavity is perfused with fluids designed to nourish the retina. In preliminary studies vitreoperfusion prevented retinal damage despite severe ischemia. Combined inner and outer retinal ischemia induced by extreme intraocular pressure elevation will be studied in cats with previous vitrectomylensectomy. The alterations of the retina will be characterized and quantitated both during and one week after a period of severe ischemia. The methods of assessment include light and electron microscopy, electroretinography, and energy metabolism measurements. Energy metabolism will be evaluated in a new way based on vitreoperfusion. The rates of O2 and glucose utilization and CO2, H+, and lactate production will be measured. They can be calculated from the concentration differences between the ingoing and outgoing vitreoperfusion fluids, since only the vitreous fluid is available for nourishment or waste removal when the ocular blood flow is negligible. We will use a two-pronged thrust to improve and clarify the effect of vitreoperfusion on ischemic retinal injury. First, we will extend our evaluation of vitreoperfusion as currently employed by determining: 1) the natural course of ischemic injury, 2) the efficacy of vitreoperfusion in preventing ischemic injury during ischemia of various durations, and 3) the ability of vitreoperfusion to reverse ischemic injury and prevent reperfusion injury after variable periods of untreated ischemia. Second, determinants of retinal survival will be sought. This will help us to understand ischemic damage and enable us to modify our vitreoperfusion technique to enhance its efficacy. By altering the composition of the vitreoperfusion fluid, we will assess the significance of O2, glucose, hypothermia, K+, Ca++, and vitamin E in retinal survival. These studies will elucidate the pathophysiologic mechanisms of retinal ischemic injury and explore a new treatment modality which potentially could be applied clinically.